Lehman A M, Schultz K R, Poskitt K, Bjornson B, Keyes R, Waters P J, Clarke L A, Everett R, McConnell D, Stockler S
Department of Medical Genetics, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.
Neuropediatrics. 2009 Aug;40(4):189-91. doi: 10.1055/s-0029-1243189. Epub 2010 Feb 4.
Infantile-onset Krabbe disease results from a deficiency of the lysosomal enzyme galactocerebrosidase and leads to death from profound central and peripheral demyelination. Neonatal hematopoietic cell transplantation may result in near-normal cognitive development and partial rescue of gross motor development. The long-term course of the disorder for treated patients seems to involve slowly progressive neurological impairment. We describe the detailed 3-year outcomes of this experimental procedure using umbilical cord blood in a prenatally-diagnosed newborn with Krabbe disease. Substantial perivascular calcifications and atrophy of the white matter developed in the first year post-transplantation. Despite persistent neuroradiological and electrophysiological evidence of leukodystrophy, at age 3 years she has had only mildly impaired non-motor development and moderately impaired motor skills. The cause of these severe white matter changes may have been due to ongoing Krabbe disease or to effects of the chemotherapy regimen or to an interaction of these factors. Extended long-term follow-up of children neonatally transplanted for Krabbe disease is needed before the full utility and limitations of neonatal transplantation can be determined.
婴儿期发病的克拉伯病是由于溶酶体酶半乳糖脑苷脂酶缺乏所致，会因严重的中枢和外周脱髓鞘而导致死亡。新生儿造血细胞移植可能会使认知发育接近正常，并部分挽救粗大运动发育。接受治疗的患者该疾病的长期病程似乎涉及缓慢进展的神经功能损害。我们描述了在一名产前诊断为克拉伯病的新生儿中使用脐带血进行这一实验性治疗的3年详细结果。移植后第一年出现了大量血管周围钙化和白质萎缩。尽管持续存在脑白质营养不良的神经放射学和电生理证据，但在3岁时，她的非运动发育仅轻度受损，运动技能中度受损。这些严重白质变化的原因可能是由于克拉伯病持续存在、化疗方案的影响或这些因素的相互作用。在确定新生儿移植的全部效用和局限性之前，需要对接受克拉伯病新生儿移植的儿童进行长期随访。
